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1.
Nano Lett ; 24(14): 4082-4090, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38526914

RESUMEN

The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (∼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to ∼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.

2.
Anal Chem ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38324754

RESUMEN

Nanozymes with multiple functionalities endow biochemical sensing with more sensitive and efficient analytical performance by widening the sensing modes. Meanwhile, the target-oriented design of multifunctional nanozymes for certain biosensing remains challenging. Herein, a constructive strategy of doping iron into polymer dots (PDs) to achieve nanozymes with excellent oxidase-mimicking and peroxidase-mimicking activity is proposed. Compared with the Fe-free PDs prepared under the same mild condition, the Fe-doped PDs (Fe-PDs) exhibit greatly boosted fluorescence at 500 nm. While applying 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate, the fluorescence of the Fe-PDs can be further quenched by oxTMB due to the inner filter effect (IFE). Inspired by this, a simple but efficient colorimetric and fluorometric dual-mode sensing platform is developed for monitoring the reducing substances ascorbic acid (AA), α-glucosidase (α-Glu), and its inhibitors (AGIs). We believe that such multifunctional enzyme-mimic materials will provoke the exploration of multimode sensing strategy with strong practicality to serve as a versatile tool in biochemical sensing.

3.
Angew Chem Int Ed Engl ; 63(15): e202400453, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38323751

RESUMEN

Aggregation-induced emission (AIE) shows promising performance in chemical sensing relying on the change of the emission behavior of the probe molecule monomers to the aggregated product. However, whether the response contrast could be further boosted by utilizing the emission property of the aggregated probe and the aggregated product remains a big challenge. Here, an exciting AIE probe regulation strategy was proposed by coherently modulating the aggregation behavior and the intramolecular charge transfer (ICT) property of the probes and thus an aggregated-to-aggregated colorimetric-fluorescent dual-mode detection was achieved. The blue emissive film obtained with the optimal AIE probe has been proven to be effective to recognize the vapor of nerve agent analog DCP in air by emitting a sharp green fluorescence. In addition, a porous polymer-based wet sensing chip loaded with the probe enables the immediate response to DCP vapor with a limit of detection (LOD) of 1.7 ppb, and it was further integrated into a wearable watch device for long-term monitoring of DCP vapor up to two weeks. We expect the present probe design strategy would greatly deepen the AIE-based science and provide new insights for long-term monitoring sensors toward trace hazardous substances.


Asunto(s)
Colorantes Fluorescentes , Agentes Nerviosos , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia , Colorimetría
4.
Anal Chem ; 94(25): 9184-9192, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35713422

RESUMEN

Although a set of functional molecules with the D-π-A structure has been explored as optical probes for the detection of target analytes, it remains a great challenge to elaborately design a single probe for distinguishing different analytes by their intrinsic oxidation or reduction capabilities and thus to generate distinct optical responses. Here, a unique TCF-based probe (DMA-CN) containing two unsaturated double bonds in the π-conjugation bridge and TCF with different reaction activities that could be cut off by KMnO4 and NaClO in varying degrees was developed, causing remarkably distinguishable responses for both fluorescence and colorimetric channels to discriminate KMnO4 and NaClO from each other. The fluorescence and colorimetric limits of detection (LODs) of the proposed DMA-CN toward KMnO4 were calculated as 60 and 91 nM, respectively, while those for NaClO were 13.3 and 214 nM, and all the optical signal change can be observed within 1 s with good specificity. Based on the proposed probe design strategy, a well-fabricated test strip was proven to be promising for the rapid, in-field detection and risk management. We expect that the present probe design methodology would provide a powerful strategy for efficient probe exploration, especially for discriminating the substances with similar oxidizing properties.


Asunto(s)
Colorimetría , Oxidantes , Colorimetría/métodos , Límite de Detección , Oxidación-Reducción
5.
Anal Chem ; 94(33): 11679-11687, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35948453

RESUMEN

Inhibition of twisting intramolecular charge transfer (TICT) is one of the most attractive methods for fluorescence-on analysis, whereas it remains enigmatic whether the fluorescence in a TICT-based probe could be thoroughly lightened. Here, for maximizing the fluorescence-on signal of the TICT-based probe, we develop a model by employing chemical reaction to directly cleave the linkage between the rotational electron donor and acceptor with a predisposed fluorescent signal close to zero. To validate this assumption, a nonfluorescent probe with barrierless rotation is successfully achieved by grafting acryloyl with -C═C- recognition sites onto coumarin, and 7-hydroxycoumarin with bright blue fluorescence could be released within 3 s upon probing KMnO4 with an amount as low as 0.95 nM and 6.6 pg. We believe that the present strategy could not only deepen the insights of photochemistry but also facilitate the development of a theranostic drug delivery system, energy conversion, pollution control, and health risk reduction.


Asunto(s)
Colorantes , Fluorescencia , Fotoquímica , Rotación
6.
Int J Mol Sci ; 23(18)2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36142353

RESUMEN

The rapid growth of the global population has resulted in a considerable increase in the demand for food crops. However, traditional crop breeding methods will not be able to satisfy the worldwide demand for food in the future. New gene-editing technologies, the most widely used of which is CRISPR/Cas9, may enable the rapid improvement of crop traits. Specifically, CRISPR/Cas9 genome-editing technology involves the use of a guide RNA and a Cas9 protein that can cleave the genome at specific loci. Due to its simplicity and efficiency, the CRISPR/Cas9 system has rapidly become the most widely used tool for editing animal and plant genomes. It is ideal for modifying the traits of many plants, including food crops, and for creating new germplasm materials. In this review, the development of the CRISPR/Cas9 system, the underlying mechanism, and examples of its use for editing genes in important crops are discussed. Furthermore, certain limitations of the CRISPR/Cas9 system and potential solutions are described. This article will provide researchers with important information regarding the use of CRISPR/Cas9 gene-editing technology for crop improvement, plant breeding, and gene functional analyses.


Asunto(s)
Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Animales , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Productos Agrícolas , Edición Génica/métodos , Genoma de Planta , Fitomejoramiento , ARN Guía de Kinetoplastida , Tecnología
7.
BMC Musculoskelet Disord ; 22(1): 525, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098919

RESUMEN

BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann's disease is an atypical type of Scheuermann's disease accompanied by Schmorl's nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann's disease is unclear, genetic and environmental factors are likely. CASE PRESENTATION: Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl's nodes. CONCLUSIONS: This is the first reported case of OI coexisting with the spinal presentation of Scheuermann's disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann's disease. In conclusion, this case demonstrates the relationship between Scheuermann's disease and OI for the first time and enriches the genotype-phenotype spectrum of OI.


Asunto(s)
Desplazamiento del Disco Intervertebral , Osteogénesis Imperfecta , Enfermedad de Scheuermann , Adulto , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Humanos , Masculino , Mutación , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/diagnóstico por imagen , Osteogénesis Imperfecta/genética
8.
Hepatology ; 69(6): 2414-2426, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30341767

RESUMEN

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina Glargina/uso terapéutico , Liraglutida/uso terapéutico , Metformina/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Fosfato de Sitagliptina/uso terapéutico , Adulto , Anciano , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Comorbilidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Modelos Lineales , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento
9.
Angew Chem Int Ed Engl ; 58(28): 9551-9555, 2019 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-31094046

RESUMEN

Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L-1 day-1 ). Other oxidase activities, such as C-C bond desaturation, aromatization, and C-C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.


Asunto(s)
Ingeniería de Proteínas/métodos , Quinolinas/química , Oxidación-Reducción
10.
Plant Mol Biol ; 97(1-2): 113-130, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29736762

RESUMEN

KEY MESSAGE: Expression analyses revealed that floral transition of Rosa odorata var. gigantea is mainly regulated by VRN1, COLs, DELLA and KSN, with contributions by the effects of phytohormone and starch metabolism. Seasonal plants utilize changing environmental and developmental cues to control the transition from vegetative growth to flowering at the correct time of year. This study investigated global gene expression profiles at different developmental stages of Rosa odorata var. gigantea by RNA-sequencing, combined with phenotypic characterization and physiological changes. Gene ontology enrichment analysis of the differentially expressed genes (DEGs) between four different developmental stages (vegetative meristem, pre-floral meristem, floral meristem and secondary axillary buds) indicated that DNA methylation and the light reaction played a large role in inducing the rose floral transition. The expression of SUF and FLC, which are known to play a role in delaying flowering until vernalization, was down-regulated from the vegetative to the pre-floral meristem stage. In contrast, the expression of VRN1, which promotes flowering by repressing FLC expression, increased. The expression of DELLA proteins, which function as central nodes in hormone signaling pathways, and probably involve interactions between GA, auxin, and ABA to promote the floral transition, was well correlated with the expression of floral integrators, such as AGL24, COL4. We also identified DEGs associated with starch metabolism correlated with SOC1, AGL15, SPL3, AGL24, respectively. Taken together, our results suggest that vernalization and photoperiod are prominent cues to induce the rose floral transition, and that DELLA proteins also act as key regulators. The results summarized in the study on the floral transition of the seasonal rose lay a foundation for further functional demonstration, and have profound economic and ornamental values.


Asunto(s)
Flores/metabolismo , Rosa/metabolismo , Flores/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Redes y Vías Metabólicas/genética , Fotoperiodo , Reguladores del Crecimiento de las Plantas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Rosa/genética , Rosa/crecimiento & desarrollo , Estaciones del Año , Análisis de Secuencia de ADN , Almidón/metabolismo , Azúcares/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
11.
BMC Pregnancy Childbirth ; 18(1): 468, 2018 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-30526530

RESUMEN

BACKGROUND: Resistance to thyroid hormone beta (RTHß) results in symptoms of both increased and decreased thyroid hormone action. The effect of thyroid hormone changes in different types of autoimmune thyroid disease (AITD) in RTHß is dynamic. CASE PRESENTATION: A 25-year-old Asian female had a RTHß Y321C mutation with Hashimoto's thyroiditis and type 2 diabetes mellitus. She was followed-up through gestation and two years postpartum, revealing development of postpartum thyroiditis (PPT) with characteristic wide fluctuations in serum thyrotropin levels, and of spontaneous recovery from an episode of transient hypothyroidism. The presence of RTHß did not prolong thyroiditis duration nor progressed toward permanent hypothyroidism. Prenatal genetic analysis was not performed on the unaffected fetus, and did not result in congenital hypothyroidism, possibly because maternal free thyroxine (FT4) levels were mildly elevated at less than 50% above the reference range in early gestation and gradually decreased to less than 20% after the 28th gestational week. CONCLUSION: In RTHß patients with autoimmune thyroid disease, episodes of thyroid dysfunction can significantly alter thyrotropin levels. During pregnancy, mildly elevated maternal free thyroxine levels less than 20% above the upper limit may not be harmful to unaffected fetuses. Unnecessary thyroid hormone control and fetal genetic testing was avoided during the gestational period with monthly follow-up.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Enfermedad de Hashimoto/metabolismo , Hipotiroidismo/metabolismo , Tiroiditis Posparto/metabolismo , Complicaciones del Embarazo/metabolismo , Embarazo en Diabéticas/metabolismo , Síndrome de Resistencia a Hormonas Tiroideas/metabolismo , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Enfermedad de Hashimoto/complicaciones , Humanos , Hipotiroidismo/etiología , Mutación , Embarazo , Receptores beta de Hormona Tiroidea/genética , Síndrome de Resistencia a Hormonas Tiroideas/complicaciones , Tiroiditis Autoinmune , Tirotropina/metabolismo , Tiroxina/metabolismo , Triyodotironina/metabolismo
12.
Int J Mol Sci ; 19(2)2018 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-29360732

RESUMEN

Plants facing the seasonal variations always need a growth restraining mechanism when temperatures turn down. C-repeat binding factor (CBF) genes work essentially in the cold perception. Despite lots of researches on CBFs, the multiple crosstalk is still interesting on their interaction with hormones and dormancy-associated MADS (DAM) genes in the growth and dormancy control. Therefore, this study highlights roles of PmCBFs in cold-induced dormancy from different orgens. And a sense-response relationship between PmCBFs and PmDAMs is exhibited in this process, jointly regulated by six PmCBFs and PmDAM4-6. Meantime, GA3 and ABA showed negative and positive correlation with PmCBFs expression levels, respectively. We also find a high correlation between IAA and PmDAM1-3. Finally, we display the interaction mode of PmCBFs and PmDAMs, especially PmCBF1-PmDAM1. These results can disclose another view of molecular mechanism in plant growth between cold-response pathway and dormancy regulation together with genes and hormones.


Asunto(s)
Frío , Epistasis Genética , Regulación de la Expresión Génica de las Plantas , Fitocromo/metabolismo , Proteínas de Plantas/genética , Prunus/fisiología , Estaciones del Año , Estrés Fisiológico/genética , Secuencia de Aminoácidos , Clonación Molecular , Expresión Génica , Especificidad de Órganos/genética , Filogenia , Reguladores del Crecimiento de las Plantas/biosíntesis , Reguladores del Crecimiento de las Plantas/genética , Proteínas de Plantas/metabolismo , Tallos de la Planta/genética , Tallos de la Planta/metabolismo , Mapeo de Interacción de Proteínas , Transporte de Proteínas , Análisis de Secuencia de ADN
13.
Cell Physiol Biochem ; 41(1): 413-421, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28214843

RESUMEN

BACKGROUND: The migration of cardiac fibroblasts to the infarct region plays a major role in the repair process after myocardial necrosis or damage. However, few studies investigated whether early hypoxia in cardiomyocytes induces the migration of cardiac fibroblasts. The purpose of this study was to assess the role of metabolites of early hypoxic cardiomyocytes in the induction of cardiac fibroblast migration. METHODS: Neonatal rat heart tissue was digested with a mixture of trypsin and collagenase at an appropriate ratio. Cardiomyocytes and cardiac fibroblasts were cultured via differential adhesion. The cardiomyocyte cultures were subjected to hypoxia for 2, 4, 6, 8, 10, and 12 h. The supernatants of the cardiomyocyte cultures were collected to determine the differences in cardiac fibroblast migration induced by hypoxic cardiomyocyte metabolites at various time points using a Transwell apparatus. Meanwhile, ELISA was performed to measure TNF-α, IL-1ß and TGF-ß expression levels in the cardiomyocyte metabolites at various time points. RESULTS: The metabolites of hypoxic cardiomyocytes significantly induced the migration of cardiac fibroblasts. The induction of cardiac fibroblast migration was significantly enhanced by cardiomyocyte metabolites in comparison to the control after 2, 4, and 6 h of hypoxia, and the effect was most significant after 2 h. The expression levels of TNF-α, IL-1ß, IL-6, and TGF-ß were substantially increased in the metabolites of cardiomyocytes, and neutralization with anti-TNF-α and anti-IL-1ß antibodies markedly reduced the induction of cardiac fibroblast migration by the metabolites of hypoxic cardiomyocytes. CONCLUSION: The metabolites of early hypoxic cardiomyocytes can induce the migration of cardiac fibroblasts, and TNF-α and IL-1ß may act as the initial chemotactic inducers.


Asunto(s)
Hipoxia de la Célula , Medios de Cultivo Condicionados/farmacología , Fibroblastos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Animales , Anticuerpos Neutralizantes/inmunología , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/citología , Fibroblastos/metabolismo , Interleucina-1beta/análisis , Interleucina-1beta/inmunología , Interleucina-6/análisis , Miocitos Cardíacos/citología , Ratas , Factor de Crecimiento Transformador beta/análisis , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/inmunología
14.
Cell Physiol Biochem ; 35(1): 213-26, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25591764

RESUMEN

BACKGROUND/AIMS: Hypoxia is a basic pathological challenge that is associated with numerous cardiovascular disorders including aberrant cardiac remodeling. Transforming growth factor beta (TGF-ß) signaling pathway plays a pivotal role in mediating cardiac fibroblast (CF) function and cardiac fibrosis. Recent data suggested that microRNA-101a (miR-101a) exerted anti-fibrotic effects in post-infarct cardiac remodeling and improved cardiac function. This study aimed to investigate the potential relationship between hypoxia, miR-101a and TGF-ß signaling pathway in CFs. METHODS AND RESULTS: Two weeks following coronary artery occlusion in rats, the expression levels of both TGFß1 and TGFßRI were increased, but the expression of miR-101a was decreased at the site of the infarct and along its border. Cultured rat neonatal CFs treated with hypoxia were characterized by the up-regulation of TGFß1 and TGFßRI and the down-regulation of miR-101a. Delivery of miR-101a mimics significantly suppressed the expression of TGFßRI and p-Smad 3, CF differentiation and collagen content of CFs. These anti-fibrotic effects were abrogated by co-transfection with AMO-miR-101a, an antisense inhibitor of miR-101a. The repression of TGFßRI, a target of miR-101a, was validated by luciferase reporter assays targeting the 3'UTR of TGFßRI. Additionally, we found that overexpression of miR-101a reversed the improved migration ability of CFs and further reduced CF proliferation caused by hypoxia. CONCLUSION: Our study illustrates that miR-101a exerts anti-fibrotic effects by targeting TGFßRI, suggesting that miR-101a plays a multi-faceted role in modulating TGF-ß signaling pathway and cardiac fibrosis.


Asunto(s)
Hipoxia de la Célula , Fibroblastos/metabolismo , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Animales , Movimiento Celular , Proliferación Celular , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Regulación hacia Abajo , Fibroblastos/citología , Fibrosis/genética , Masculino , MicroARNs/antagonistas & inhibidores , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/citología , Miocardio/patología , Oligonucleótidos Antisentido/metabolismo , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Ratas , Ratas Sprague-Dawley , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/química , Receptores de Factores de Crecimiento Transformadores beta/genética , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba
15.
BMC Med Genet ; 16: 76, 2015 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-26329403

RESUMEN

BACKGROUND: The autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are caused by interactions between susceptibility genes and environmental triggers. Single nucleotide polymorphisms (SNPs) of Solute carrier family 22, member 4 (SLC22A4) have been shown to be associated with several autoimmune diseases, including Crohn's disease (CD) and rheumatoid arthritis (RA). The aim of this study is to investigate whether SNP rs3792876 in the SLC22A4 gene is associated with GD, HT and AITD in a Chinese Han population. METHODS: In this study, we collected specimens from 553 Chinese Han individuals of 92 AITD pedigrees in 10 cities in Liaoning province, China (80 GD pedigrees, 478 members; 12 HT pedigrees, 75 members). SNP rs3792876 was genotyped using the TaqMan allelic discrimination assay. Hardy-Weinberg Equilibrium tests were performed among founders of the pedigrees using Haploview software. Family-based association tests performed using FBAT software. RESULTS: No deviation from Hardy-Weinberg equilibrium was observed (p > 0.05). There were not significant association between the SLC22A4 gene polymorphism (rs3792876) and GD, HT and AITD was found. CONCLUSIONS: These results suggest a lack of association between the SLC22A4 gene polymorphism rs3792876 and susceptibility to GD, HT and AITD in a Chinese Han population.


Asunto(s)
Pueblo Asiatico/genética , Enfermedades Autoinmunes/genética , Proteínas de Transporte de Catión Orgánico/genética , Polimorfismo de Nucleótido Simple/genética , Enfermedades de la Tiroides/genética , Enfermedades Autoinmunes/etnología , Técnicas de Genotipaje , Humanos , Simportadores , Enfermedades de la Tiroides/etnología
16.
Bioconjug Chem ; 26(1): 110-9, 2015 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-25506713

RESUMEN

Dual endosomal pH-sensitive micelles were designed and fabricated to deliver doxorubicin (DOX) for treating breast cancer based on a poly(2-ethyl-2-oxazoline) (PEOz)-DOX (PEOz-hyd-DOX) conjugate. PEOz-hyd-DOX was successfully synthesized by connecting DOX to PEOz via an acid cleavable hydrazone linker and self-assembled into nanosized micelles, which further physically encapsulated DOX. The conjugate and DOX-loaded conjugate micelles displayed faster release of DOX at pH 5.0 than at pH 7.4. This pH-dependent release behavior might assist the quick diffusion of DOX from acidic endosomes or lysosomes and the intracellular transfer into the nucleus after internalization, which was confirmed by confocal laser scanning microscopy images. As expected, PEOz-hyd-DOX conjugate and DOX-loaded conjugate micelles maintained cytotoxicity of DOX. In addition, the dual endosomal pH-sensitive micelles were found to substantially enhance antitumor efficacy and reduce side effects compared with free DOX. Therefore, PEOz-hyd-DOX conjugate-based micelles might be potential drug delivery vehicles of DOX for safe and effective breast cancer therapy.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Doxorrubicina/química , Doxorrubicina/farmacología , Endosomas/efectos de los fármacos , Micelas , Poliaminas/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Transporte Biológico , Doxorrubicina/síntesis química , Doxorrubicina/metabolismo , Liberación de Fármacos , Endosomas/metabolismo , Femenino , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Ratones , Ratones Desnudos , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Pharm Res ; 32(8): 2649-62, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25676595

RESUMEN

PURPOSE: The purpose of the present study was to design and fabricate endosomal pH-sensitive dual-ligand-modified micellar nanoparticles to achieve enhanced drug delivery to tumor cells and facilitated intracellular drug release. METHODS: End-group-carboxylated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) and cyclic Arg-Gly-Asp-Tyr-Lys- and anti-prostate specific membrane antigen antibody-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) were synthesized and characterized by (1)H NMR and gel permeation chromatography, and self-assembled into micelles. Paclitaxel-loaded dual-ligand-modified micelles were prepared by thin-film hydration method, and characterized by dynamic light scattering, transmission electron microscope, pH-dependent in vitro release and stability. Intracellular paclitaxel delivery was measured by flow cytometry and imaged by confocal microscopy. In vitro cytotoxicity was studied in the 22Rv1 xenograft prostate tumor cell lines. RESULTS: The prepared dual-ligand-modified micelles with about 30 nm in diameter and rapid intracellular drug release behavior at endo/lysosomal pH were very effective in enhancing the cytotoxicity of paclitaxel against 22Rv1 cells by increasing the cellular uptake, which was verified the correlation with the expression of integrin αvß3 and prostate specific membrane antigen in tumor cells by flow cytometric analysis and confocal microscopy, compared with single ligand-modified micelles. CONCLUSION: These findings provided valuable information that the application of combining of dual-ligand modifications with pH-sensitivity to polymeric micelles may be a promising approach in the efficient delivery of anticancer drugs for treatment of integrin αvß3 and prostate specific membrane antigen expressing prostate cancers.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Anticuerpos/administración & dosificación , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Concentración de Iones de Hidrógeno , Integrina alfaVbeta3/metabolismo , Luz , Masculino , Micelas , Nanopartículas , Poliaminas , Poliésteres , Antígeno Prostático Específico/inmunología , Dispersión de Radiación , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Endocr J ; 61(12): 1181-90, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25242258

RESUMEN

As Th22 subsets are identified, their involvement in the pathogenesis of numerous autoimmune diseases has become apparent. In this study, we investigated differentiation of Th22 cells in the autoimmune thyroid diseases including Hashimoto's thyroiditis (HT) and Graves' disease (GD). Besides, we also explored the involvement of Th22 cells in an iodine-induced autoimmune thyroiditis (AIT) model (i.e., NOD.H-2(h4) mice). In HT patients, we showed the level of circulating Th22 cells correlated with the level of serum IL-22, and was significantly higher than in GD patients and healthy control subjects. Levels of serum IL-6, a major Th22 cell differentiation effector, were also higher in HT, and correlated with Th22 cells concentration. Peripheral blood mononuclear cells isolated from HT patients produced larger amounts of IL-6 in vitro than did those isolated from other groups. Furthermore, unlike those from GD patients, T lymphocytes from HT patients showed an enhanced differentiation in vitro into Th22 cells in the presence of recombinant IL-6 and TNF-α. In addition, levels of circulating Th22 cells and titers of thyroid peroxidase antibody were positively correlated in HT patients. In NOD.H-2(h4) mice, higher numbers of Th22 cells were observed in the spleens of the AIT group, while splenocytes of this group also produced larger amounts of IL-6 and IL-22 in vitro compared with the control. Intra-thyroid infiltrating IL-22+ lymphocytes were significantly increased in mice of the AIT group compared with the control. Our results indicate that Th22 cells may contribute to the pathogenesis of HT.


Asunto(s)
Autoinmunidad , Linfocitos T CD4-Positivos/patología , Enfermedad de Hashimoto/patología , Interleucinas/metabolismo , Linfopoyesis , Tiroiditis Autoinmune/patología , Regulación hacia Arriba , Adulto , Animales , Autoanticuerpos/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Femenino , Enfermedad de Graves/sangre , Enfermedad de Graves/inmunología , Enfermedad de Graves/metabolismo , Enfermedad de Graves/patología , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/metabolismo , Humanos , Interleucina-6/sangre , Interleucina-6/metabolismo , Interleucinas/sangre , Yoduro Peroxidasa/antagonistas & inhibidores , Masculino , Ratones Endogámicos NOD , Distribución Aleatoria , Bazo/inmunología , Bazo/metabolismo , Bazo/patología , Glándula Tiroides/inmunología , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Tiroiditis Autoinmune/sangre , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/metabolismo , Interleucina-22
19.
Microorganisms ; 12(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38674646

RESUMEN

Crude oil gasification bacteria, including fermenting bacteria, hydrocarbon-oxidizing bacteria, reducing bacteria, and methanogenic bacteria, participate in multi-step reactions involving initial activation, intermediate metabolism, and the methanogenesis of crude oil hydrocarbons. These bacteria degrade crude oil into smaller molecules such as hydrogen, carbon dioxide, acetic acid, and formic acid. Ultimately, they convert it into methane, which can be utilized or stored as a strategic resource. However, the current challenges in crude oil gasification include long production cycles and low efficiency. This paper provides a summary of the microbial flora involved in crude oil gasification, the gasification metabolism pathways within reservoirs, and other relevant information. It specifically focuses on analyzing the factors that affect the efficiency of crude oil gasification metabolism and proposes suggestions for improving this efficiency. These studies deepen our understanding of the potential of reservoir ecosystems and provide valuable insights for future reservoir development and management.

20.
Animal Model Exp Med ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38873827

RESUMEN

BACKGROUND: The aim of this study was to investigate the influence of marking methods on the outcomes of body composition analysis and provide guidance for the selection of marking methods in mouse body composition analysis. METHODS: Male C57BL/6J mice aged 6 weeks were randomly assigned for pre- and post- ear tagging measurements. The body composition of the mice was measured using a small animal body composition analyzer, which provided measurements of the mass of fat, lean, and free fluid. Then, the mass of fat, lean and free fluid to body weight ratio was gained. Further data analysis was conducted to obtain the range and coefficient of variation in body composition measurements for each mouse. The distribution of fat and lean tissue in the mice was also analyzed by comparing the fat-to-lean ratio. RESULTS: (1) The mass of all body composition components in the ear tagging group was significantly lower than that in the control group. (2) There was a significant increase in the range and coefficient of variation of body composition measurements between the ear tagging group and the control group. (3) The fat-to-lean ratio in the ear tagging group was significantly lower than that in the control group. CONCLUSIONS: Ear tagging significantly lowered the results of body composition analysis in mice and higher the results of measurement error. Therefore, ear tagging should be avoided as much as possible when conducting body composition analysis experiments in mice.

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